Objective To observe and explore the clinical effect of oral administration of traditional Chinese medicine decoction in patients with uremic pruritus during high-flux hemodialysis. Methods A total of 94 patients with uremic pruritus admitted to our hospital from January to December 2022 were selected as the research objects. According to the different treatment methods, they were divided into the routine group (treated with high-flux hemodialysis) and the combined group (treated with high-flux hemodialysis combined with traditional Chinese medicine decoction), with 47 patients in each group. The clinical efficacy, skin pruritus (UP-Dial score), serological indicators (HA, 5-5-HT, CRP, IL-2, IL-8) and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the combined group was 97.87%, which was higher than 80.85% in the conventional group, and the difference was statistically significant (P <0.05). After treatment, the UP-Dial score, HA, 5-HT, CRP, IL-2 and IL-8 in the two groups were lower than those before treatment, and the combined group was lower than the conventional group, the differences were statistically significant (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion Oral administration of traditional Chinese medicine decoction in the treatment of uremia patients with high-flux hemodialysis can further reduce the symptoms of skin itching, improve clinical efficacy, enhance antihistamine effect, down-regulate the expression of 5-HT and inflammatory factors, with high safety and certain clinical application value.